About OMICS Group

1. About OMICS Group OMICS Group is an amalgamation of Open Access publications and worldwide international science conferences and events. Established in the year 2007 with the sole aim of making the information on Sciences and technology ‘Open Access’, OMICS Group publishes 500 online open access scholarly journals in all aspects of Science, Engineering, Management and Technology journals. OMICS Group has been instrumental in taking the knowledge on Science & technology to the doorsteps of ordinary men and women. Research Scholars, Students, Libraries, Educational Institutions, Research centers and the industry are main stakeholders that benefitted greatly from this knowledge dissemination. OMICS Group also organizes 500 International conferences annually across the globe, where knowledge transfer takes place through debates, round table discussions, poster presentations, workshops, symposia and exhibitions.

2. About OMICS International Conferences OMICS International is a pioneer and leading science event organizer, which publishes around 500 open access journals and conducts over 500 Medical, Clinical, Engineering, Life Sciences, Pharmascientific conferences all over the globe annually with the support of more than 1000 scientific associations and 30,000 editorial board members and 3.5 million followers to its credit. OMICS Group has organized 500 conferences, workshops and national symposiums across the major cities including San Francisco, Las Vegas, San Antonio, Omaha, Orlando, Raleigh, Santa Clara, Chicago, Philadelphia, Baltimore, United Kingdom, Valencia, Dubai, Beijing, Hyderabad, Bengaluru and Mumbai.

3. Dr Sergey Suchkov, MD, PhD Professor in Immunology & Medicine I.M.Sechenov First Moscow State Medical University and A.I.Evdokimov Moscow State Medical & Dental University, Moscow, Russia ISPM(International Society for Personalized Medicine), Tokyo, Japan PMC (Personalized Medicine Coalition), Washington, USA EPMA (European Association for Predictive, Preventive and Personalized Medicine), Brussels, EU PPPM as an Avenue to Predict and to Prevent Chronic Disorders Dr Eduard Charchyan, MD, PhD Professor in Medicine Head, Division for Cardiovascular Surgery, B.V.Petrovskii National Center for Surgery, Russian Academy of Sciences, Moscow, Russia DrYuriiBelov, MD, PhD Professor in Medicine Director, B.V.Petrovskii National Center for Surgery, Russian Academy of Sciences, Moscow, Russia

4. Over the course of its history, medicine has given special attention to the already diseased individual, focusing on a type of disorder (nosology) rather than on one’s health or the so-called pre-illnessconditions, the latter being left in the shade. The link that might exert reliable control over morbidity, mortality and disabling rates and significantly optimize the cost of treatment for those who had fallen ill! The name of the link is Predictive, Preventive and Personalized Medicine (Fig).

5. PPPM associated with Subclinical and Predictive Diagnostics

6. To achieve the practical implementation of PPPM concept, it is necessary to create a fundamentally new strategy based upon the pre-early (subclinical) recognition of biomarkers of hidden imbalances and defects long before the illness clinically manifests itself. This strategy would give a real opportunity to secure preventive measures whose personalization could have a significantly positive influence on demographics! (Fig)

7. Impacts to be assumed for the practical implementation of PPPM into the practice

8. Human cardiovascular disease is a consequence of a complex interplay of genetic, epigenetic and environmental factors. Conventional cardiology attempts to prevent disease by modifying established risk factors and to treat manifest disease, often after complications have occurred and irreversible tissue changes have taken place. Current therapies (eg, those for heart failure) are administered uniformly across a heterogeneous spectrum of disease etiology, severity and genetic background. Now we have the opportunity to expand our medical armamentarium to include molecular phenotypes (signatures) that distinguish subtle subclassifications of disease and allow us to better tailor both prevention strategies and therapeutics.

9. PPPM as thus the big change to forecast, to predict and to prevent is rooted in a big and new science to be rooted from the achievements of genomics, proteomics, metabolomics andbioinformatics whichare being implemented into the daily practice to secure visualizing of lesion foci that was previously unknown to clinicians (Fig. x2)

12. In reality, Genomics as a setofmoleculartools toprobegenomeandtothusidentifyand toselectgenomicbiomarkers has allowed for identifying newer genetic variations that affect health to form subclinical and predictive risks to be screened and unveiled, and then the subclinicalpathology to be diagnosed, monitored and terminated to preventillness

14. Over the last decade genome-wide association studies (GWASs) have identified many loci associated with late-onset cardiovascular diseases including coronary artery disease, and correlates of myocardial function. Genetic loci with multiple trait associations have also provided novel biological insights. For example, of the 46 genetic loci associated with coronary artery disease, only 16 are also associated with conventional risk factors for cardiovascular disease whereas the remaining two thirds reflect novel pathways.

15. Well, genes can say a lot about an individual’s predisposition to a disease, but cannot reveal what is happening in cells at the protein level. The latter would attribute to proteomics to identify individual proteins to be valuable for predictive diagnosing and thus may eventually have a great impact on PPPM Predictive & Prognostic Diagnosing Predictive & Prognostic Diagnosing Predictive & Prognostic Diagnosing

16. Meanwhile, a combination of genomicand proteomic biomarkers are becoming of great significance to predict risks of the chronificationand thus of disabling since chronic cardiovascular diseases are preceded by a long subclinical (symptom-free) phase or a period of latency

17. In reality, proteomics per se isthe continuation of functional genomics and, at the same time, a prologue to metabolomics Genome Proteome 106 human proteins 25,000 human genes Proteome Genome Transcriptomic modifications Posttranslational modifications (PTMs) of proteins Alternative splicing (mRNA) Metabolome Transcriptome

18. The latter (metabolomics) illustrates the functional state of the cell at the level of metabolism on a real time basis, requiring the use of the term 'metabolome', demonstrating a set of metabolic pathwaysin the cell at a given time point

19. Tissue-derived information we would accumulate might be combined withthe: ● individual's medical records; ● family history; ● data from imaging; ●instrumental and laboratory tests to develop personalizedandpreventivetreatments. But, in this sense, how is the whole databank provided by omics-technologies could be comprehended?

20. It is bioinformatics to suit the goal by applying mathematical modeling techniques to thus secure constructing and maintaining unified biobanksand databanks necessary for personal health monitoring based on principles of genotyping and phenotyping. As a result, the patient becomes a data carrier, whilst learning about possible risks of a disease, and the physician can reasonably select a kind of preventive and personalized protocol rooting from the predictive assays made (Fig).

21. By integrating bioinformatics and clinical informatics, both offers unique infrastructure, tools, techniques and applications to bridge those areas. This facilitates the sharing of data and information across diverse disciplines and professional sectors

22. Individuals, selected in the first (genotypic) stage, undergo the second stage, which uses a panel of phenotypic biomarkers, whilst monitoring every: ● potential patients, ● persons-at-risks predisposed to the disease, and/or ● persons at subclinical stages of the disease.

23. PPPM will require the integration of clinical information, stable and dynamic genomics, and molecular phenotyping. Bioinformatics will be crucial in translating these data into useful applications, leading to improved diagnosis, prediction, prognostication and treatment. So, our viewpoint would support the contributions of genomic and proteomic approaches in developing a preventive and personalized approach to cardiovascular medicine.

24. In the era of personalized medicine there is increased interest in the incorporation of individual biomarkers in risk score algorithms in order to improve cardiovascular risk stratification followed by the prompt initiation of preventive measures whilst evaluated the predictive and prognostic value of currently used biomarkers like cardiac troponins, non-HDL-cholesterol, apolipoproteins, natriuretic peptides (NPs) as well as promising future biomarkers like copeptin, choline and lipoprotein-associated phospholipase A2 (LP-PLA2). For instance, galectin-3 is an active biomarker of mortality!

25. Galectin-3

26. Meanwhile, ST2 is released by stressed cardiac myocytes and also predicts mortality in myocardial infarction.

27. ST-2

28. Copeptin is a stable arginine vasopressin precursor associated with increased risk of heart failure to be used to exclude acute myocardial infarction

29. Copeptin

30. Most of the latter are directly associated with development of atherosclerotic cardiovascular disease. So, we would need absolute proofs to confirm clinical applications of the biomarkers mentioned, evaluating not only their diagnostic and prognostic value but also their integrability into routine practice Although a single biomarker is a tangible entity that can be easily understood, aggregate measures comprised of multiple genes are also informative as the combinatorial biomarkers.

31. The simultaneous addition of combinatorial biomarkers of cardiovascular substantially improves the risk stratification for death from cardiovascular causes beyond that of a model that is based only on established risk factors. And clinical potential may be evaluated by asking three fundamental questions: (1) Can the clinician measure the biomarker as applicable to cardiac diseases? (2) Does it add new information? (3) Does it help the cardiologist to manage patients? The incorporation of the multiplexed but consolidated biomarkers mentioned into clinical practice for the prediction of death from cardiovascular causes could be accomplished quickly, since the measurement of these biomarkers is already well established for diagnostic use.

32. The greatest limitation in personalizing cardiovascular medicine today is our inability to accurately predict risk for patients. For instance, myocardial infarction results as a consequence of atherosclerotic plaque rupture, with plaque stability largely depending on the lesion forming extracellular matrix components. Meanwhile, MMP-1 serum levels was found to be an independent biopredictorfor coronary atherosclerotic lesions, while not allowing a stratification of plaque morphology. Correlation between MMP-1 serum levels and total plaque burden

33. Molecular Imaging as applicable to Cardiology

34. Cellular targets for molecular imaging agents

35. In vivo MRI of human thrombi using a fibrin-targeting peptide conjugated to gadolinium–tetraazacyclododecanetetraaceticacid (a) MRI before contrast enhancement (b) EP-2104R injection causes signal enhancement and visualization of left ventricular thrombus (arrow) (c) In a different patient, the post-EP-2104R image shows signal enhancement corresponding to aortic thrombus (arrow) (d) Corresponding contrast-enhanced CT shows atherosclerotic plaque with calcification (arrowhead). Abbreviations: LV, left ventricle; RV, right ventricle. With kind permission from Springer Science + Business Media: European Radiology, MR imaging of thrombi using EP-2104R, a fibrin-specific contrast agent: initial results in patients

36. Integrating High-Throughput Measurements with the Phenotype: from Science to Medicine (Omenn& Athey, NCIBI, 2010)

37. Multifactorial risk factor modification and control • can have a profound and favorable impact on • decreasing the incidence of initial and recurrent cardiovascular events. • Meanwhile, because the adult heart has negligible regenerative capacity, healing of the infarcted myocardium is dependent on sequential activation of inflammatory and fibrogenic signals. • So, a strategy of preventive treatment should contain, • at least, two critical steps for postmyocardial infarction: • quenching of inflammation and degeneration; and, • restoration of the tissue affected.

38. Look, acute cardiomyocyte necrosis in the infarcted heart generates Damage-Associated Molecular Patterns (DAMPs) (Fig. x2)

39. Initiation of the inflammatory response following myocardial infarction Necrotic cardiomyocytes (CM) and damaged extracellular matrix release danger signals (DAMPS) triggering the complement cascade and activating TLR/IL-1 signaling. Leukocytes, in turn, are recruited in the infarcted heart through activation of a multi-step adhesion cascade

40. Resolution of the post-infarction inflammatory response involves activation of multiple inhibitory signals and recruitment, or transdifferentiation, of leukocyte subsets with suppressive properties

41. The geometric, functional and molecular alterations associated with post-infarction remodeling are driven by the inflammatory cascade and are involved in the development of heart failure. So, we would have to treat but better to prevent! The implementation of cardiovascular prevention strategies continues to reduce the incidence of myocardial infarction. What should we do and which kinds of the preventive protocols could be exploited?

42. Prevention can be divided into 3 types: ● primordial (prevention of risk factors); ● primary (treatment of risk factors); ● secondary (prevention of recurrent cardiovascular events)

43. Therapeutic potential of HDL in cardioprotectionand tissue repair HDL may improve cardiac function in several ways: ● may protect the heart against ischaemia/reperfusion injury resulting in a reduction of infarct size and thus in myocardial salvage. ● can improve cardiac function in the absence of ischaemic heart disease. ● may improve cardiac function by reducing infarct expansion and by attenuating ventricular remodeling post-myocardial infarction These different mechanisms are substantiated by in vitro, ex vivo, and in vivo intervention studies that applied the treatment mentioned

44. MMP-2 Matrix metalloproteinase (MMPs) MMPs are long understood to be involved in remodeling of the extracellular matrix. MMP-2 proteolyzes components of the sarcomere, and its intracellular activity contributes to ischemia-reperfusion injury of the heart.

45. RNA interference therapy may achieve in vivo biomedical imaging and targeted therapy.

46. Targeting B cells in atherosclerosis Atherosclerotic plaque formation is strongly influenced by different arms of the immune system, including B lymphocytes. B1 cells are atheroprotective mainly via the production of natural IgM antibodies that bind oxidized low-density lipoprotein and apoptotic cells. B2 cells are suggested to be proatherogenic. Thus, B cells represent a novel interesting target for therapeutic modulation of the atherosclerotic disease process

47. Targeting Wnt signaling to improve wound healing after myocardial infarction

48. Meanwhile, regenerating the human heart is a challenge that has engaged clinicians around the globe for nearly a century. Exciting progress has been made to establish cell transplantation techniques in recent years, and I would discuss briefly cell therapy approaches for heart regeneration. The human heart harbors an adult stem cell population consistent with true characteristics of stemness such as self-renewal, clonogenicity, and multilineage differentiation potential. Recent evidence demonstrates the ability of resident human cardiac cells to differentiate into mechanically integrated cardiomyocytes as well as vascular smooth muscle and endothelial cells, thereby supporting cardiac regeneration. Adoptive transfer of human cardiac stem cells results in modest repair due in part to lack of survival, proliferation, and commitment of the transplanted cells after myocardial infarction. For instance, transplanted human CD34+ cells augment capillary formation, inhibit myocardial fibrosis and preserve left ventricular (LV) function in myocardial infarction. Moreover, exploitation of bone marrow–derived SCs effectively demonstrate improved cardiac function after transplantation of stem cells (Fig).

50. Moreover, modification of human cardiac progenitor cells (hCPCs) to enhance proliferation, survival, and commitment increases effectiveness of stem cells as a viable therapeutic modality. Ex vivo genetic modification is an effective strategy to enhance stem cell function. Transplantation of bioengineered cardiac cells and tissue patches containing either progenitor cells or cardiomyocytes for cardiac repair is emerging as an exciting treatment option for patients with postinfarction left ventricular (LV) remodeling. The beneficial effects may evolve directly from remuscularization or indirectly through mechanisms that mobilize and/or activate endogenous progenitor cells to promote neovascularization and remuscularization, inhibit apoptosis, and attenuate LV dilatation and disease progression.